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J Thorac Cardiovasc Surg 2000;120:923-934
© 2000 The American Association for Thoracic Surgery

General Thoracic Surgery

A novel approach with magnetic resonance imaging used for the detection of lung allograft rejection

From the Department of Biological Sciences and Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University,^a and the Department of Surgery, University of Pittsburgh,^b Pittsburgh, Pa.

Supported by research grants from the National Institutes of Health (R01RR-10962 and R01RR/AI-15187) and The Whitaker Foundation. The experiments were performed in the Pittsburgh NMR center for Biomedical Research, which is supported by a grant (P41RR-03631) from the National Center for Research Resources as an NIH-supported Resource Center.

Received for publication May 4, 2000. Revisions requested June 6, 2000., revisions received June 14, 2000. Accepted for publication June 29, 2000. Address for reprints: Chien Ho, PhD, Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Ave, Pittsburgh, PA 15213-2683 (E-mail: chienho{at}andrew.cmu.edu).

Abstract

Objective: Although various techniques have been explored for the detection and quantification of allograft transplant rejection, a practical and reliable method that is noninvasive is still elusive.
Methods: For our magnetic resonance imaging experiments, we have developed a new rat model of heterotopic lung transplantation to the inguinal region. Allogeneic transplants (DA to Brown Norway) were performed with and without cyclosporine A (INN: ciclosporin) treatment, with syngeneic transplants (Brown Norway to Brown Norway) serving as controls (n = 6 per group). Magnetic resonance images were obtained with a gradient echo method before and after injection of ultra-small superparamagnetic iron oxide particles.
Results: At day 5, allogeneic transplants without cyclosporine A treatment showed a grade 4 rejection histologically. A significantly lower magnetic resonance signal was seen 24 hours after injection of ultra-small superparamagnetic iron oxide particles compared with the preinjection image (346 ± 7.6 vs 839 ± 43.4 arbitrary units; P < .05). Syngeneic transplants showed no evidence of rejection histologically and no differences in magnetic resonance imaging signals between the images before and after injection of ultra-small superparamagnetic iron oxide particles (863 ± 18.8 vs 880 ± 22.5). Allotransplants treated with cyclosporine A showed a grade 2 rejection histologically. The change in magnetic resonance signals in that group was small but showed a significant decrease in signal intensity after injection (646 ± 10.5 vs 889 ± 23.5, P < .05). Immunohistochemistry and iron staining of the allografts indicated that ultra-small superparamagnetic iron oxide particles were taken up by the infiltrating macrophages that accumulated at the rejection site.
Conclusions: We have demonstrated a novel approach for the detection of acute lung allograft rejection using magnetic resonance imaging coupled with injection of ultra-small superparamagnetic iron oxide particles. Despite its limitations, our method might be a first step toward a potential clinical application.

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